Pd‐PEPPSI Complexes and the Negishi Reaction

An overview of Pd‐PEPPSI complexes in the Negishi cross‐coupling reaction is presented. Preliminary evaluations of differentially substituted imidazolium salts that generate highly active cross‐coupling catalysts in situ provide the foundation for the development of an air‐ and moisture‐stable NHC‐based precatalyst: Pd‐PEPPSI‐IPr. The application of Pd‐PEPPSI‐IPr in sp 3 –sp 3 , sp 3 –sp 2 (and vice versa), and sp 2 –sp 2 Negishi cross‐couplings is reviewed. This allowed the systematic development of Pd‐PEPPSI‐IPent, a more sterically demanding, second‐generation catalyst that outperforms the IPr analogue in a variety of sp 2 –sp 2 Negishi cross‐couplings. General routes for the preparation of organozinc reagents are also examined, and an additives study reveals the probable transmetallating species that is operative in these cross‐couplings. Mechanistic considerations of the Negishi cross‐coupling reaction based on experimental and computational studies are summarized and evaluated.